This application is for the Competing Renewal of an Institutional NRSA for combined MD and PhD training in the Medical Scientist Training Program (MSTP) at Harvard Medical School (HMS) and the Massachusetts Institute of Technology (MIT). The purpose of this training program is to meet an overwhelming need for physician scientists who will lead the translation of new research discoveries into improvements in human health. The program offers an integrated course of study combining medical education at HMS with graduate study at Harvard or MIT. For medical education, HMS offers a choice of two different programs leading to the MD degree: a problem-solving, case-based approach to learning that incorporates patient exposure and case scenarios from the onset of medical school (New Pathway), or a curriculum that emphasizes quantitative analysis and technology taught jointly with MIT (Health Sciences and Technology). For graduate study, the scope of scientific training in the program ranges from the basic sciences to translational research and bioengineering to the social sciences. The medical and scientific training components are integrated throughout the program, beginning with a course in the Molecular Biology of Human Disease and a laboratory research rotation that are taken by all MSTP students during the summer before the first academic year. The resources available to meet this mission are outstanding, including facilities and faculty from 10 pre-clinical departments at HMS, HMS-appointed faculty in both preclinical and clinical departments at seven different Harvard-affiliated teaching hospitals and institutes, and the many academic departments in the basic and social sciences at the main campuses of Harvard University and MIT in Cambridge. Students are provided guidance from before matriculation through to the end of their training by advisors with specific expertise in their area of research interest. Multiple MD-PhD-specific curricular activities foster strong relationships among each cohort and across multiple cohorts of students. 169 faculty members participate directly in the program through service on program committees and/or participation as MD-PhD student thesis advisors. The trainees are exceptionally qualified and diverse. Although not all MD-PhD students are awarded funding at the time of matriculation, the program is designed to include all students at Harvard Medical School who choose to simultaneously pursue the MD and PhD degrees, offering all program activities and mentoring support to 155 current MD-PhD students whether MSTP-funded or not. MSTP funds leverage considerable support from other training grants, individual NIH investigator awards, individual student fellowships, departmental funds, hospital funds and unrestricted institutional funds. PUBLIC HEALTH RELEVANCE The purpose of this training program is to meet an overwhelming need for physician scientists who will lead the translation of new research discoveries into improvements in human health. The program offers students the largest collection of academic laboratories in the world for research training, complemented by teaching hospitals in position to rapidly translate basic discoveries into new clinical applications. Upon completion of the training program, graduates will be poised to become future leaders in biomedical discovery, in the development of next generation diagnostic tools and therapeutics, and in shaping strategies for maximizing the clinical impact of these new discoveries.